Transcript Athersclerosis

Atherosclerosis
 hardening of the arteries due to the
deposition of atheromas
 heart disease is the leading cause of death
 caused by the deposition of cholesteryl esters
on the walls of arteries
 atherosclerosis is correlated with high LDL
and low HDL
Hyperlipidemia
 How does atherosclerosis start?
 Complex process of damage
to the inner layer of the artery
(endothelium)
 Elevated levels of lipids
in the blood
 High blood pressure
 Tobacco smoke
What is Hypercholesterolemia
Is a high level of cholesterol in the
blood that can cause plaque to form
and build up leading to blockages in the
arteries (arteriosclerosis)
increasing the risk for heart attack,
stroke, circulation problems, and death.
Normal Arterial Wall
Tunica adventitia
Tunica media
Tunica intima
Endothelium
Subendothelial connective
tissue
Internal elastic membrane
Smooth muscle cell
Elastic/collagen fibres
External elastic membrane
How it affects your body
 High Cholesterol Causes Arteriosclerosis
The arteriosclerosis, involves several steps.
 (1) The innermost lining of the arteries (the endothelium)
is damaged or becomes dysfunctional and cholesterol
particles deposit into the damaged wall.
 (2) The cholesterol becomes incorporated into a mixture
called plaque, which is composed of cholesterol, other
fatty substances, fibrous tissue, and calcium.
 (3) As more cholesterol and other substances
incorporate, the plaque grows, narrowing the artery .
CONT…
 (4) Plaque build-up can grow large enough to
impede blood flow through the artery (called a
"blockage").
 When the arteries supplying the heart with blood
are blocked, chest pain (angina) may occur.
 when arteries in the legs are blocked, leg pain or
cramping may occur; when arteries supplying the
brain with blood are blocked, stroke may occur
 . If the plaque ruptures, a blood clot may develop
on top of it. If the blood clot completely blocks
blood flow through a coronary artery, it may result
in a heart attack (myocardial infarction);
Pathogenesis of Atherosclerotic
Endothelial damage
Plaques
Protective response results in production of
cellular adhesion molecules
Monocytes and T lymphocytes attached to
‘sticky’ surface of endothelial cells
Migrate through arterial wall to subendothelial space
Macrophages take up oxidised LDL cholesterol
Lipid-rich foam cells
Fatty streak and plaque
Photograph of an arterial plaque
Development of Atherosclerotic
Plaques
Fatty streak
Lipid rich plaque
Normal
Foam cells
Fibrous cap
Complex plaque
Lipid core
Thrombus
Factors promoting elevated blood lipids
 age
 men >45 years of age; women > 55 years of age







family history of CAD
smoking
hypertension >140/90 mm Hg
low HDL cholesterol
obesity >30% overweight
diabetes mellitus
inactivity/ lack of exercise
Treatment for Hypercholesterolemia
 There are many different ways to treat high cholesterol
like Nonpharmacological Therapy, Diet, Weight loss,
Exercise, &Pharmacological(Drug) therapy
 Standard nonpharmacological therapy mostly consists
of adjusting to eating and exercise habits.
 lowers the LDL cholesterol level by about 30 mg/dL.
 Diet minimizes extra cholesterol and fat intake,
especially saturated fat.
 Weight Loss, even if losing 5-10lbs. of weight can double
the reduction in LDL levels achieved through a diet.
CONT…
 Statins lower LDL cholesterol levels by
20%-40%. If someone takes maximum
doses, they lower LDL levels by 40%-50%.
 They get a benefit of increasing the
amount of HDL ("good") cholesterol level
in the body by about 5%-10%.
Dyslipidemia & Exercise
 Generally, dyslipidemia does not alter the
exercise response
 Regular participation in physical activity can
manifest beneficial changes
 Lowering TG concentrations
 Increase HDL concentrations
 Increase in enzyme activity in lipoprotein
metabolism (LPL, HL)
 Exercise can (in)directly improve profiles
Relationship of Serum Cholesterol to Mortality
(Seven Countries Study)
Death rate from CHD/1000 men
35
Northern Europe
30
25
United States
20
15
Southern Europe, inland
10
Serbia
Southern Europe, Mediterranean
5
Japan
0
2.60
3.25
3.90
4.50
5.15
5.80
6.45
7.10
7.75
8.40
9.05
Serum total cholesterol (mmol/l)
(Adapted from Verschuren et al.,)
Symptoms of Hyperholesterolemia
 High cholesterol rarely causes symptoms. It is usually
detected during a regular blood test that measures
cholesterol levels.
 Being diagnosed with conditions that may be caused in
part by high cholesterol (such as arteriosclerosis,
coronary artery block, and stroke) may be the first clue
that a person has high cholesterol.
 For example:

The first symptom of coronary artery disease (CAD)
is often chest pain (angina). Chest pain may occur during
activities that increase the heart rate.
Cont…
 However, many people have CAD for several years
without symptoms.
 Unless the person has a transient ischemic attack
(TIA).
 Some people with lipid disorders or familiall
hypercholesterolemia may have other distinct
symptoms such as deposits of excess cholesterol
that collect in the skin or eye tissue.
 These cholesterol deposits can also cause nodules
in tendons in the hands or feet or rarely yellow
streaks in the hands.
HDL: A Major Risk Factor for CHD
 A low plasma HDL is an important risk factor for
CHD in the general population
 A high level of HDL may confer cardioprotection
 Reverse cholesterol transport by HDL may be the
principle cardioprotective mechanism
On average, a 10% decrease in CHD risk
occurs for each increase of 4 mg/dL in the
HDL level.
The ILIB Lipid Handbook for Clinical Practice. 1995:26.
HDL in Clinical Practice
 Routinely measured in all adult patients
 HDL-C <35 mg/dL is a major risk factor
 Nonpharmacologic therapy (exercise, weight
loss, smoking cessation)
 Pharmacologic therapy
Consider drug therapy that lowers LDL-C
and also increases HDL-C levels.
Expert Panel. JAMA. 1993;269:3015-3023.
The Role of
Small, Dense LDL
as a CHD Risk Factor
Atherogenicity of Small, Dense LDL
Endothelial
Chemoattractants
LDL
Monocyte
Endothelium
Macrophag
e
LDL
Mildly oxidized
Macrophage
Smooth
Muscle Cell
Foam Cell
Highly oxidized
Evidence from in vitro studies suggests that large, buoyant LDL particles are
more resistant to oxidative stress and small, dense LDL particles more
susceptible to oxidation.
Role of LDL in atherosclerosis
 LDLs penetrate vascular wall, deposit in the
intima and with time are damaged by oxidation.
 Oxidised LDLs attract the attention of
macrophages which ingest the LDL.
 Macrophages become overloaded with lipid and
become “foam” cells which die and release pools
of lipid in the vessel wall (plaques).
Cont…
 A complex processes mediated by
cytokines and growth factors causes
smooth muscle cells to form a
collagenous cap over the lipid (mature
atherosclerotic plaque).
 Cap grows and can constrict the vessel
(causing angina for example).
Cont…
 Macrophages can degrade the cap while T




cells can inhibit collagen synthesis – the cap
can rupture to expose collagen and lipids
This leads to aggregation of platelets and
blood clot formation.
If the coronary artery is blocked by a clot –
heart attack.
Blocking of arteries in the brain causes
stroke.
Antioxidants (vitamin E and C) may protect
LDL from oxidation and so protect against
heart attack and stroke.
Clinical Manifestations of Atherosclerosis

Coronary heart disease


Cerebrovascular disease


Angina pectoris, myocardial infarction, sudden
cardiac death
Transient ischaemic attacks, stroke
Peripheral vascular disease

Intermittent claudication, gangrene